Getting specificity from simplicity in putative proteins from the prebiotic Earth

doi:10.1073/pnas.0706876104

Getting specificity from simplicity in putative proteins from the prebiotic Earth

*Instituto de Química Física “Rocasolano,” Consejo Superior de Investigaciones Científicas, Serrano 119, 28006 Madrid, Spain; and
^†Departments of Medical Biophysics and Biochemistry, University of Toronto, Toronto, ON, Canada M5G-2M9

Communicated by Robert L. Baldwin, Stanford University Medical Center, Stanford, CA, July 26, 2007 (received for review April 20, 2007)

Abstract

Can unique protein structures arise from a limited set of amino acids present on the prebiotic Earth? To address this question, we have determined the stability and structure of KIA7, a 20-residue polypeptide containing chiefly Lys, Ile, and Ala. NMR methods reveal that KIA7 tetramerizes and folds on the millisecond time scale to adopt a four-helix X-bundle structure with a tightly and specifically packed core. Denaturation studies and hydrogen exchange measurements of KIA7 and several variants demonstrate that ridges-into-grooves packing of Ala and Ile side chains and the packing of a C-terminal aromatic group into the hydrophobic core are sufficient to give rise to a rather stable, well folded protein structure, with no favorable electrostatic interactions or tertiary or quaternary hydrogen bonds. Both modern proteins and RNAs can adopt specific structures, but RNAs do so with a limited “alphabet” of residues and types of stabilizing interactions. The results reported here show that specific, well folded protein structures can also arise from a highly reduced set of stabilizing interactions and amino acids that are thought to have been present on the prebiotic Earth.

Footnotes

^‡To whom correspondence may be addressed. E-mail: chakrab{at}uhnres.utoronto.ca or dlaurents{at}iqfr.csic.es
Author contributions: J.L.d.l.O., C.G., A.C., and D.V.L. designed research; J.L.d.l.O., C.G., and D.V.L. performed research; D.A.B., S.H., and A.C. contributed new reagents/analytic tools; J.L.d.l.O., C.G., A.C., and D.V.L. analyzed data; and J.L.d.l.O., C.G., A.C., and D.V.L. wrote the paper.
The authors declare no conflict of interest.
Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB ID codes 2jo4 and 2jo5).
This article contains supporting information online at www.pnas.org/cgi/content/full/0706876104/DC1.
Freely available online through the PNAS open access option.